Hu Yihan, Deeba Elie, Kläppe Ulf, Öijerstedt Linn, Andersson John, Ruffin Nicolas, Piehl Fredrik, Ingre Caroline, Fang Fang, Seitz Christina
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
Brain Behav Immun Health. 2024 Nov 22;42:100907. doi: 10.1016/j.bbih.2024.100907. eCollection 2024 Dec.
Amyotrophic lateral sclerosis (ALS) represents a complex syndrome characterized by motor, psychiatric, and cognitive symptoms, where associations between cellular immune features and non-motor manifestations remain unknown.
In this cohort study, we enrolled 250 incident people with ALS (pwALS) assessed with the Hospital Anxiety and Depression Scale, and 226 pwALS with the Montreal Cognitive Assessment, including 218 overlapping pwALS. All individuals were diagnosed between January 2015 and January 2023 in Stockholm, Sweden. We applied joint latent class models to delineate distinct trajectories of anxiety, depression, and cognition, incorporating survival outcomes. A majority of the pwALS had data on leukocyte counts and flow cytometric analyses using a comprehensive T cell panel. We then used immune cell subtypes measured at diagnosis to predict trajectories of these outcomes following ALS diagnosis.
We identified two distinct trajectories for anxiety, depression, and cognitive function following ALS diagnosis. PwALS with longer survival displayed more stable trajectories, while those with shorter survival showed decreasing anxiety symptom, increasing depressive symptom, and declining cognitive function. Higher count of leukocytes at the time of ALS diagnosis tended to associate with anxiety and depression trajectories related to shorter survival. Among T cell subpopulations, several CD8 T cell subsets were associated with a stable trajectory of depressive symptom, and, in turn, better survival.
ALS-associated psychiatric and cognitive trajectories vary significantly between pwALS with different prognosis. Certain T cell subsets measured at diagnosis might be indicative of depression trajectories post-diagnosis.
肌萎缩侧索硬化症（ALS）是一种复杂的综合征，其特征为运动、精神和认知症状，而细胞免疫特征与非运动表现之间的关联尚不清楚。
在这项队列研究中，我们纳入了250例新发ALS患者（pwALS），使用医院焦虑抑郁量表进行评估，以及226例使用蒙特利尔认知评估量表的pwALS患者，其中包括218例重叠的pwALS患者。所有个体于2015年1月至2023年1月在瑞典斯德哥尔摩被诊断。我们应用联合潜在类别模型来描绘焦虑、抑郁和认知的不同轨迹，并纳入生存结果。大多数pwALS患者有白细胞计数数据以及使用综合T细胞面板进行的流式细胞术分析数据。然后，我们使用诊断时测量的免疫细胞亚型来预测ALS诊断后这些结果的轨迹。
我们确定了ALS诊断后焦虑、抑郁和认知功能的两种不同轨迹。生存时间较长的pwALS表现出更稳定的轨迹，而生存时间较短的患者则表现出焦虑症状减轻、抑郁症状加重和认知功能下降。ALS诊断时白细胞计数较高往往与生存时间较短的焦虑和抑郁轨迹相关。在T细胞亚群中，几个CD8 T细胞亚群与抑郁症状的稳定轨迹相关，进而与更好的生存相关。
与ALS相关的精神和认知轨迹在预后不同的pwALS患者之间存在显著差异。诊断时测量的某些T细胞亚群可能指示诊断后的抑郁轨迹。
